6-Guanidinopyranoses: Novel Carbohydrate Based Peptidomimetics

Angewandte Chemie (International Edition in English)

Volumn 36, Issue 7, 1997, Pages 751-752

  Wessel, Hans Peter ^a   Banner, David ^a   Gubernator, Klaus ^a   Hilpert, Kurt ^a   Müller, Klaus ^a   Tschopp, Thomas ^a  

^a F HOFFMANN LA ROCHE LTD   (Switzerland)

Author keywords

Carbohydrates; Enzyme inhibitors; Guanidino sugars; Peptidomimetics

Indexed keywords

EID: 0030809269     PISSN: 05700833     EISSN: None     Source Type: Journal    
DOI: 10.1002/anie.199707511     Document Type: Article

References (22)

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10. 2Ph), 3.50 (ddd ≈ dt, 1 H, H-3), 3.49 (m, 1 H, H-5), 3.40 (m, 2H, H- 6) 3.l7 (ddd ≈ dt, 1 H, H-2), 3.02 (ddd ≈ dt, 1H, H-4).
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13. 2Ph), 4.19 (dd, J(2.3) = 9.7 Hz, 1 H, H-2), 3.64 (ddd ≈ dt, J(3.3-OH) = 6.0 Hz, J(3.4) = 8.9 Hz, 1H; H3), 3.56 (ddd, J(5,6a) = 3.0 Hz. J(5,6b) = 5.8 Hz, H-5), 3.40, 3.32 (2dd, 2H, H-6), 3.09 (ddd ≈ dt, J(4.4-OH) = 6.5 Hz, J(4,5) = 9.6 Hz, 1H, H-4).
14. Crystals of the complex of human thrombin with 8 were prepared, and data measured to 3.3 Å̊ resolution and processed as described [7,16]. With initial atomic coordinates from the best available thrombin structure, the difference electron density clearly showed the inhibitor bound in the active site. The structure was refined with tight geometrical constraints to R = 0.126 with standard deviations of 0.011 Å for bond lengths, 1.88° for bond angles, and 1.96° for torsion angles relative to standard parameters [19].
15. D. Banner, J. Ackermann, A. Gast, K. Gubernator, P. Hadváry, K. Hilpert, L. Labler, K. Múller, G. Schmid, T. Tschopp, H. van de Waterbeemd, B. Wirz in Perspectives in Medicinal Chemistry (Eds,: B. Testa, W. Fuhrer, E. Kyburz, R. Giger), VCH, Weinheim, 1993, pp. 27-43.
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19. Sugar amino acids as non-peptidic peptidomimetics have been used to constrain peptide conformations: a) H. Kessler, R. Gratias, G. Hessler, M. Gurrath, G. Müller, Pure Appl. Chem. 1996, 68, 1201-1205; b) E. Graf von Reedern, E. Lohof, G. Hessler, M. Hoffmann, H. Kessler, J. Am. Chem. Soc. 1996, 118, 10156-10167.
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